Effect of simultaneous injection of L-arginine in dorsal hippocampus and laterodorsal periaqueductal gray matter on morphine-induced analgesia in rat’s formalin test

Injection of l-arginine, a precursor of nitric oxide, in the rat’s hippocampus or periaqueductal gray matter reduces the analgesic effect of morphine on formalin-induced pain, but the effect of simultaneous injection of the substance in both areas have not been shown as our purpose of this research.

Wistar rats were used as control, morphine, and l-arginine groups. The rats were simultaneously cannulated in two areas of the dorsal hippocampus and laterodorsal PAG. One week later, the control animals received 50 μl of 2.5% formalin in the paw of the left foot under restrainer. The morphine group 10 min before formalin received the opioid (6 mg/kg, intraperitoneally). Other groups took l-arginine (0.25-2 µg/rat) in only one area (d hippocampus or ld PAG), prior to morphine administration. The effective dose of l-arginine (0.5 µg/rat) simultaneously was injected in both areas. The findings were analyzed by analysis of variance (ANOVA) under α=0.05.

Morphine induced analgesic response. Injection of NO precursor both separately and simultaneously in the two nuclei reduced morphine-induced analgesia.

Increasing levels of NO due to exclusive or concurrent injection of l-arginine in the areas likely antagonize the morphine response.